Fanconi Anemia (FA) Animal Model Service

In vivo studies are essential for Fanconi anemia (FA) research as they provide the only platform to fully recapitulate the complex systemic pathogenesis, thereby enabling critical therapeutic evaluation. Building on our pioneering expertise in FA research, Protheragen leads in developing cutting-edge animal models that provide critical insights for disease study. As your dedicated partner, we deliver robust models to ensure your research objectives are met with precision and reliability.

Overview of Fanconi Anemia (FA) Animal Models

Animal models for Fanconi anemia (FA), primarily generated through targeted disruption of genes within the FA/BRCA DNA repair pathway (such as Fanca, Fancg, and Fancd2), are indispensable pre-clinical tools that recapitulate the core pathological features of the human disease. These models reliably exhibit hallmark characteristics including progressive bone marrow failure, congenital abnormalities, and a pronounced hypersensitivity to DNA crosslinking agents like mitomycin C. Furthermore, they display a strong predisposition to the development of malignancies, particularly acute myeloid leukemia (AML) and solid tumors.

Fig.1 The humanized mouse model with endogenous Fanconi anemia (FA) mutation and high human hematopoietic stem cell chimerism. (Choo S, et al., 2025)

Our Services

As a leader in rare blood disease research, Protheragen is committed to providing comprehensive and highly specialized animal model development services for Fanconi anemia (FA). Our expertise in genetic engineering and functional validation enables us to deliver reliable, well-characterized models that accurately recapitulate the complex pathophysiology of FA, offering invaluable tools for mechanistic investigation and robust preclinical therapeutic evaluation.

Animal Models of Fanconi Anemia (FA)

Protheragen utilizes advanced gene-editing technologies, including knockout and conditional knockout strategies, to develop highly accurate Fanconi anemia (FA) animal models for preclinical research.

• Fanca Knockout Models
• Fancg Knockout Models
• Fancd2 Knockout Models

• Braca2 (Fancd1) Knockout Models
• Fanca Conditional Knockout Models
• Fancd2 Conditional Knockout Models

Featured Animal Models

Case Study-Polygenic Brca2^Δ27/Δ27 + Rad51c^dah/dah Mutant Mouse Model

Model Introduction

Fanconi anemia (FA) is a devastating genetic disorder characterized by progressive bone marrow failure and profound cancer predisposition. To address the urgent need for representative animal models that recapitulate its complex pathogenesis, we developed a novel polygenic mouse model carrying combined mutations in two critical FA pathway genes: a C-terminal truncation in Brca2 (Brca2^Δ27/Δ27) and a 6-bp deletion in Rad51c (Rad51c^dah/dah). This innovative model not only mimics the core hematopoietic defects of FA but also provides a robust and reliable platform for investigating disease mechanisms and evaluating novel therapeutic strategies.

Methodology

• Animal Model: We generated the Rad51c^dah/dah strain on an FVB/J background using gene editing technology. This model was strategically crossbred with our existing Brca2^Δ27/Δ27 strain (maintained on an SWR.129P2 background) to create the novel polygenic Brca2^Δ27/Δ27 + Rad51c^dah/dah double-mutant mice. For the current study, comprehensive phenotypic analyses were performed comparing these double-mutant mice with wild-type (WT) littermate controls.
• Phenotypic Analysis Methods: Bone marrow cellularity was assessed by direct cell counting. Peripheral blood from 8–12-week-old mice was analyzed by complete blood count (CBC) to evaluate hematopoietic lineages.

Phenotypic Analysis & Results

The Brca2^Δ27/Δ27 + Rad51c^dah/dah mice exhibited progressive hematopoietic defects consistent with Fanconi anemia (FA):

• Bone Marrow Hypocellularity: Double-mutant mice showed significantly reduced bone marrow cellularity compared to WT controls. (Fig.2A)
• Pancytopenia: CBC analysis revealed reductions in white blood cell (WBC) and red blood cell (RBC) counts in Brca2^Δ27/Δ27 + Rad51c^dah/dah double-mutant mice. (Fig.2B-C)
• Macrocytosis: Affected mice displayed enlarged red blood cells, reflecting aberrant erythropoiesis and mirroring the macrocytosis observed in FA patients. (Fig.2D)

Fig.2 Phenotypic validation of the Brca2^Δ27/Δ27 + Rad51c^dah/dah mouse model. (A) Nucleated cells per femur; (B) White blood cells; (C) Red blood cells; (D) Mean corpuscular volume. Data are presented as mean ± SEM (n=8). *p < 0.05, **p < 0.01 vs. WT.

Conclusion

This study establishes the Brca2^Δ27/Δ27 + Rad51c^dah/dah double-mutant mouse as a robust model of Fanconi anemia (FA) that faithfully recapitulates the core clinical and pathological features of the human disease. The observed bone marrow hypocellularity, significant leukopenia, and characteristic macrocytosis collectively demonstrate progressive impairment of hematopoietic function, closely mirroring the bone marrow failure trajectory in FA patients. The consistency of these phenotypic hallmarks confirms the model's validity and positions it as a valuable preclinical platform for investigating FA disease mechanisms and evaluating the efficacy of novel therapeutic strategies.

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Focusing on preclinical research, Protheragen utilizes precise animal models to enable pharmacodynamic (PD), pharmacokinetic (PK), and toxicology assessments to support the development and regulatory approval of potential therapies. If you are interested in our animal model development services, please do not hesitate to contact us for more details and quotation information.

Reference

• Choo S, Tong A H, Fields E, et al. A rescue fanconi anemia humanized mouse model with endogenous FA mutation and high human hematopoietic stem cell chimerism[J]. Molecular Therapy Methods & Clinical Development, 2025, 33(3).